The protein composition of ovarian cyst fluid has not been studied extensively. Ovarian cyst fluid from 13 benign serous or mucinous cystadenomas, 1 dermoid cyst and 2 ovarian carcinomas were analyzed by SDS polyacrylamide gel electrophoresis (SDS PAGE). In each case, 90 percent or more of the total protein was a 65,000 KD band. There was no consistent difference in the minor protein bands among the various types of cyst fluids analyzed. Conditioned serum free medium from 4 ovarian carcinoma cell lines was analyzed similarly. The protein pattern obtained was closely similar to that of the cyst fluids. Especially remarkable was the predominant 65 KD band present in vivo in the cyst fluids and in vitro in the media of the carcinoma cell lines. The migration rate on SDS PAGE of the 65 KD band is identical to human serum albumin (66 KD). Studies are in progress to further characterize and identify this protein. It is noteworthy that the ovarian carcinoma cell lines secrete the same or similar protein that is found in ovarian cyst fluids. To our knowledge, secretion of an abundant albumen-like protein by ovarian cyst lining cells in vivo and ovarian carcinoma cells in vitro has not been previously reported. Secretion of a large amount of protein by cyst lining cells may be instrumental in ovarian cyst fluid accumulation and therefore cyst enlargement.